tbuckley/cabot-search huggingface dataset:
Adverse events following first and second dose COVID-19 vaccination in England, October 2020 to September 2021: a national vaccine surveillance platform self-controlled case series study
Authors: Ruby SM Tsang, Mark Joy, Rachel Byford, Chris Robertson, Sneha N Anand, William Hinton, Nikhil Mayor, Debasish Kar, John Williams, William Victor, Ashley Akbari, Declan T Bradley, Siobhan Murphy, Dermot O’Reilly, Rhiannon K Owen, Antony Chuter, Jillian Beggs, Gary Howsam, Aziz Sheikh, FD Richard Hobbs, Simon de Lusignan
Journal: Eurosurveillance (2023)

Background Post-authorisation vaccine safety surveillance is well established for reporting common adverse events of interest (AEIs) following influenza vaccines, but not for COVID-19 vaccines. Aim To estimate the incidence of AEIs presenting to primary care following COVID-19 vaccination in England, and report safety profile differences between vaccine brands. Methods We used a self-controlled case series design to estimate relative incidence (RI) of AEIs reported to the national sentinel network, the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub. We compared AEIs (overall and by clinical category) 7 days pre- and post-vaccination to background levels between 1 October 2020 and 12 September 2021. Results Within 7,952,861 records, 781,200 individuals (9.82%) presented to general practice with 1,482,273 AEIs, 4.85% within 7 days post-vaccination. Overall, medically attended AEIs decreased post-vaccination against background levels. There was a 3–7% decrease in incidence within 7 days after both doses of Comirnaty (RI: 0.93; 95% CI: 0.91–0.94 and RI: 0.96; 95% CI: 0.94–0.98, respectively) and Vaxzevria (RI: 0.97; 95% CI: 0.95–0.98). A 20% increase was observed after one dose of Spikevax (RI: 1.20; 95% CI: 1.00–1.44). Fewer AEIs were reported as age increased. Types of AEIs, e.g. increased neurological and psychiatric conditions, varied between brands following two doses of Comirnaty (RI: 1.41; 95% CI: 1.28–1.56) and Vaxzevria (RI: 1.07; 95% CI: 0.97–1.78). Conclusion COVID-19 vaccines are associated with a small decrease in medically attended AEI incidence. Sentinel networks could routinely report common AEI rates, contributing to reporting vaccine safety.
COVID-19 mortality attenuated during widespread Omicron transmission, Denmark, 2020 to 2022
Authors: Nikolaj U Friis, Tomas Martin-Bertelsen, Rasmus K Pedersen, Jens Nielsen, Tyra G Krause, Viggo Andreasen, Lasse S Vestergaard
Journal: Eurosurveillance (2023)

BackgroundIt sparked considerable attention from international media when Denmark lifted restrictions against COVID-19 in February 2022 amidst widespread transmission of the new SARS-CoV-2 Omicron variant and a steep rise in reported COVID-19 mortality based on the 30-day COVID-19 death count.AimOur aim was to investigate how coincidental infections affected COVID-19 mortality estimates following the introduction of the Omicron variant in late 2021.MethodsWe compared the 30-day COVID-19 death count with the observed mortality using three alternative mortality estimation methods; (i) a mathematical model to correct the 30-day COVID-19 death count for coincidental deaths, (ii) the Causes of Death Registry (CDR) and (iii) all-cause excess mortality.ResultsThere was a substantial peak in the 30-day COVID-19 death count following the emergence of the Omicron variant in late 2021. However, there was also a substantial change in the proportion of coincidental deaths, increasing from 10-20% to around 40% of the recorded COVID-19 deaths. The high number of 30-day COVID-19 deaths was not reflected in the number of COVID-19 deaths in the CDR and the all-cause excess mortality surveillance.ConclusionOur analysis showed a distinct change in the mortality pattern following the introduction of Omicron in late 2021 with a markedly higher proportion of people estimated to have died with, rather than of, COVID-19 compared with mortality patterns observed earlier in the COVID-19 pandemic. Our findings highlight the importance of incorporating alternative mortality surveillance methods to more correctly estimate the burden of COVID-19 as the pandemic continues to evolve.
Minimal invasiveness in nonsurgical periodontal therapy
Authors: Fernanda V. Ribeiro, Jaimini J. Mehta, Mabelle F. Monteiro, Jatinder Moore, Marcio Z. Casati, Luigi Nibali
Journal: Periodontology 2000 (2023)

Abstract Periodontal treatment is quickly moving towards a philosophy consisting of a less invasive approach. In this context, minimally invasive nonsurgical therapy (MINST) is a promising option. This paper reviews the concepts behind minimal invasiveness in nonsurgical periodontology and reports the state‐of the art evidence for this topic. Instruments used and protocols suggested for these applications are introduced and discussed. The original papers reviewed show probing pocket depth (PPD) reductions and clinical attachment level (CAL) gains ranging from 2 to 4 mm between baseline and 6 months to 5 years posttreatment for intrabony defects and from 1.5 to 3 mm between baseline and 2‐6 months of follow‐up for full‐mouth results. These clinical outcomes are accompanied by statistically significant reductions in radiographic bone defect depth and increases in intrabony defect angles posttreatment. Wound healing mechanisms following MINST are presented, and clinical applications and directions for future research are suggested.
Periodontal microbiology and microbial etiology of periodontal diseases: Historical concepts and contemporary perspectives
Authors: Georgios N. Belibasakis, Daniel Belstrøm, Sigrun Eick, Ulvi K. Gursoy, Anders Johansson, Eija Könönen
Journal: Periodontology 2000 (2023)

Abstract This narrative review summarizes the collective knowledge on periodontal microbiology, through a historical timeline that highlights the European contribution in the global field. The etiological concepts on periodontal disease culminate to the ecological plaque hypothesis and its dysbiosis‐centered interpretation. Reference is made to anerobic microbiology and to the discovery of select periodontal pathogens and their virulence factors, as well as to biofilms. The evolution of contemporary molecular methods and high‐throughput platforms is highlighted in appreciating the breadth and depth of the periodontal microbiome. Finally clinical microbiology is brought into perspective with the contribution of different microbial species in periodontal diagnosis, the combination of microbial and host biomarkers for this purpose, and the use of antimicrobials in the treatment of the disease.
MOF‐Immobilized Two‐in‐One Engineered Enzymes Enhancing Activity of Biocatalytic Cascade for Tumor Therapy
Authors: Caiqi Yang, Wen Liu, Shanfeng Chen, Xiaoqing Zong, Pengfei Yuan, Xinjie Chen, Xiaodi Li, Yuchao Li, Wei Xue, Jian Dai
Journal: Advanced Healthcare Materials (2023)

Abstract Biocatalytic systems based on enzyme cascade reactions have attracted growing interest in the field of biocatalytic medicine. However, it is a major challenge to reasonably construct enzyme cascade reactions with high stability, selectivity, and catalytic efficiency for the in vivo biocatalytic application. Herein, two‐in‐one engineered glucose oxidase (GOx‐Fe 0 ) is fabricated by a biomineralization strategy, through which a nanozyme (Fe 0 NP) is anchored within the inner cavity of GOx. Then, GOx‐Fe 0 is immobilized in a pH‐sensitive metal–organic framework (MOF) zeolitic imidazolate framework‐8 (ZIF‐8) to establish a stable and effective MOF‐immobilized two‐in‐one engineered enzyme, GOx‐Fe 0 @ZIF‐8. In vitro studies show that GOx‐Fe 0 @ZIF‐8 exhibits excellent stability and high pH/glucose selectivity, and the shorter spacing between cascade enzymes can increase the cascade throughput and effectively improve the reaction efficiency of the enzyme cascade. In vivo experiments exhibit that GOx‐Fe 0 @ZIF‐8 solves the instability and systemic toxicity of free enzymes, and achieves deep tumor penetration and significant chemodynamic therapeutic efficacy through a pH/glucose‐selective enzyme cascade reaction in tumor site. Taken together, such an orchestrated enzyme engineering strategy can effectively improve enzyme stability, selectivity, and enzyme cascade reaction efficiency via chemical transformations, and also provide a promising strategy for the application of biocatalytic cascade reactions in vivo.
The impact of depression and anxiety on the risk of exacerbation in adults with bronchiectasis: a prospective cohort study
Authors: Yong-Hua Gao, Hui-Zhen Zheng, Hai-Wen Lu, Yuan-Yuan Li, Yun Feng, Bei Mao, Jiu-Wu Bai, Shuo Liang, Ke-Bin Cheng, Shu-yi Gu, Xiao-Li Sun, Jian-Xiong Li, Ai Ge, Man-Hui Li, Jia-Wei Yang, Lu Bai, Han-Yu Yu, Jie-Ming Qu, Jin-Fu Xu
Journal: European Respiratory Journal (2023)

Exacerbations significantly contribute to impaired quality of life (QoL), accelerated lung function decline and premature mortality in bronchiectasis [1]. Prevention of exacerbations is one of the key goals in international guidelines for bronchiectasis [2, 3]. Thus, identifying risk factors associated with exacerbation will be important to design and deliver the right interventions to the right people, and are an active area of research [4]. Depression was associated with an increased risk of exacerbations in patients with bronchiectasis and may be a crucial "treatable trait" for exacerbation prevention <https://bit.ly/3iCwPWa>
Respiratory management of drowning-associated acute respiratory failure: a multicentre retrospective cohort study
Authors: Florian Reizine, Yannick Fedun, Laetitia Bodenes, Pierre Bouju, Pierre Fillâtre, Aurélien Frérou, Olivier Lesieur, Arnaud Gacouin, Agathe Delbove
Journal: European Respiratory Journal (2023)

<b>Management of drowning-associated acute hypoxaemic respiratory failure remains poorly explored. In the present retrospective observational study, non-invasive ventilation and high-flow nasal cannula uses were associated with lower intubation rates.</b>https://bit.ly/3WYwNqr
Isolation of extracellular fluids reveals novel secreted bioactive proteins from muscle and fat tissues
Authors: Melanie J. Mittenbühler, Mark P. Jedrychowski, Jonathan G. Van Vranken, Hans-Georg Sprenger, Sarah Wilensky, Phillip A. Dumesic, Yizhi Sun, Andrea Tartaglia, Dina Bogoslavski, Mu A, Haopeng Xiao, Katherine A. Blackmore, Anita Reddy, Steven P. Gygi, Edward T. Chouchani, Bruce M. Spiegelman
Journal: Cell Metabolism (2023)
Errors in Figure and Tables
Journal: JAMA Network Open (2023)

Ibrahim Azar, MD; Omid Yazdanpanah, MD; Hyejeong Jang, MS; Adam Austin, MD; Seongho Kim, PhD; Jie Chi, MD; Samer Alkassis, MD; Biplab K. Saha, MD; Amit Chopra, MD; Kristoffer Neu, MD; Syed Mehdi, MD; Hirva Mamdani, MD
A Neural Coordination Strategy for Attachment and Detachment of a Climbing Robot Inspired by Gecko Locomotion
Authors: Bingcheng Wang, Zhouyi Wang, Yifan Song, Weijia Zong, Linghao Zhang, Keju Ji, Poramate Manoonpong, Zhendong Dai
Journal: Cyborg and Bionic Systems (2023)

Climbing behavior is a superior motion skill that animals have evolved to obtain a more beneficial position in complex natural environments. Compared to animals, current bionic climbing robots are less agile, stable, and energy-efficient. Further, they locomote at a low speed and have poor adaptation to the substrate. One of the key elements that can improve their locomotion efficiency is the active and flexible feet or toes observed in climbing animals. Inspired by the active attachment–detachment behavior of geckos, a hybrid pneumatic–electric-driven climbing robot with active attachment–detachment bionic flexible feet (toes) was developed. Although the introduction of bionic flexible toes can effectively improve the robot’s adaptability to the environment, it also poses control challenges, specifically, the realization of attachment–detachment behavior by the mechanics of the feet, the realization of hybrid drive control with different response characteristics, and the interlimb collaboration and limb–foot coordination with a hysteresis effect. Through the analysis of geckos’ limbs and foot kinematic behavior during climbing, rhythmic attachment–detachment strategies and coordination behavior between toes and limbs at different inclines were identified. To enable the robot to achieve similar foot attachment–detachment behavior for climbing ability enhancement, we propose a modular neural control framework comprising a central pattern generator module, a post-processing central pattern generation module, a hysteresis delay line module, and an actuator signal conditioning module. Among them, the hysteresis adaptation module helps the bionic flexible toes to achieve variable phase relationships with the motorized joint, thus enabling proper limb-to-foot coordination and interlimb collaboration. The experiments demonstrated that the robot with neural control achieved proper coordination, resulting in a foot with a 285% larger adhesion area than that of a conventional algorithm. In addition, in the plane/arc climbing scenario, the robot with coordination behavior increased by as much as 150%, compared to the incoordinated one owing to its higher adhesion reliability.
Field-Controlled Microrobots Fabricated by Photopolymerization
Authors: Xiyue Liang, Zhuo Chen, Yan Deng, Dan Liu, Xiaoming Liu, Qiang Huang, Tatsuo Arai
Journal: Cyborg and Bionic Systems (2023)

Field-controlled microrobots have attracted extensive research in the biological and medical fields due to the prominent characteristics including high flexibility, small size, strong controllability, remote manipulation, and minimal damage to living organisms. However, the fabrication of these field-controlled microrobots with complex and high-precision 2- or 3-dimensional structures remains challenging. The photopolymerization technology is often chosen to fabricate field-controlled microrobots due to its fast-printing velocity, high accuracy, and high surface quality. This review categorizes the photopolymerization technologies utilized in the fabrication of field-controlled microrobots into stereolithography, digital light processing, and 2-photon polymerization. Furthermore, the photopolymerized microrobots actuated by different field forces and their functions are introduced. Finally, we conclude the future development and potential applications of photopolymerization for the fabrication of field-controlled microrobots.
Efficacy of Dapagliflozin by Baseline Diabetes Medications: A Prespecified Analysis From the DAPA-CKD Study
Authors: Jelle M. Beernink, Frederik Persson, Niels Jongs, Gozewijn D. Laverman, Glenn M. Chertow, John J.V. McMurray, Anna Maria Langkilde, Ricardo Correa-Rotter, Peter Rossing, C. David Sjöström, Robert D. Toto, David C. Wheeler, Hiddo J.L. Heerspink
Journal: Diabetes Care (2023)

OBJECTIVE To determine whether the benefits of dapagliflozin in patients with type 2 diabetes and chronic kidney disease (CKD) in the Dapagliflozin And Prevention of Adverse Outcomes in CKD trial (DAPA-CKD) varied by background glucose-lowering therapy (GLT). RESEARCH DESIGN AND METHODS We randomized 4,304 adults (including 2,906 with type 2 diabetes) with a baseline estimated glomerular filtration rate (eGFR) 25–75 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio of 200–5,000 mg/g to dapagliflozin 10 mg or placebo once daily (NCT03036150). The primary end point was a composite of ≥50% eGFR decline, end-stage kidney disease, and kidney or cardiovascular cause of death. Secondary end points included a kidney composite end point (primary composite end point without cardiovascular death), a cardiovascular composite end point (hospitalized heart failure or cardiovascular death), and all-cause mortality. In this prespecified analysis, we investigated the effects of dapagliflozin on these and other outcomes according to baseline GLT class or number of GLTs. RESULTS The effects of dapagliflozin on the primary composite outcome were consistent across GLT classes and according to the number of GLTs (all interaction P &amp;gt; 0.08). Similarly, we found consistent benefit of dapagliflozin compared with placebo on the secondary end points regardless of background GLT class or number of GLTs. The same applied to the rate of decline in the eGFR rate and safety end points. Dapagliflozin reduced the initiation of insulin therapy during follow-up compared with placebo (hazard ratio 0.72; 95% CI 0.54–0.96; P = 0.025). CONCLUSIONS Dapagliflozin reduced kidney and cardiovascular events in patients with type 2 diabetes and CKD across baseline GLT class or classes in combination.
Alternative splicing in multiple myeloma is associated with the non-homologous end joining pathway
Authors: Enze Liu, Nathan Becker, Parvathi Sudha, Chuanpeng Dong, Yunlong Liu, Jonathan Keats, Gareth Morgan, Brian A. Walker
Journal: Blood Cancer Journal (2023)

Alternative splicing plays a pivotal role in tumorigenesis and proliferation. However, its pattern and pathogenic role has not been systematically analyzed in multiple myeloma or its subtypes. Alternative splicing profiles for 598 newly diagnosed myeloma patients with comprehensive genomic annotation identified primary translocations, 1q amplification, and DIS3 events to have more differentially spliced events than those without. Splicing levels were correlated with expression of splicing factors. Moreover, the non-homologous end joining pathway was an independent factor that was highly associated with splicing frequency as well as an increased number of structural variants. We therefore identify an axis of high-risk disease encompassing expression of the non-homologous end joining pathway, increase structural variants, and increased alternative splicing that are linked together. This indicates a joint pathogenic role for DNA damage response and alternative RNA processing in myeloma.
Rare Cause of Hypoxemia in a Toddler: New Diagnosis of Hereditary Hemorrhagic Telangiectasia
Authors: Shikha Saxena, Patrick W. Doyle, Christopher M. Baron, Thomas P. Doyle, Andrew G. Sokolow
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Rare Cause of Hypoxemia in a Toddler: New Diagnosis of Hereditary Hemorrhagic Telangiectasia." American Journal of Respiratory and Critical Care Medicine, 207(11), pp. 1533–1535
G Protein–Coupled Estrogen Receptor GPER: Molecular Pharmacology and Therapeutic Applications
Authors: Jeffrey B. Arterburn, Eric R. Prossnitz
Journal: The Annual Review of Pharmacology and Toxicology (2023)

The actions of estrogens and related estrogenic molecules are complex and multifaceted in both sexes. A wide array of natural, synthetic, and therapeutic molecules target pathways that produce and respond to estrogens. Multiple receptors promulgate these responses, including the classical estrogen receptors of the nuclear hormone receptor family (estrogen receptors α and β), which function largely as ligand-activated transcription factors, and the 7-transmembrane G protein–coupled estrogen receptor, GPER, which activates a diverse array of signaling pathways. The pharmacology and functional roles of GPER in physiology and disease reveal important roles in responses to both natural and synthetic estrogenic compounds in numerous physiological systems. These functions have implications in the treatment of myriad disease states, including cancer, cardiovascular diseases, and metabolic disorders. This review focuses on the complex pharmacology of GPER and summarizes major physiological functions of GPER and the therapeutic implications and ongoing applications of GPER-targeted compounds.
Strong peak immunogenicity but rapid antibody waning following third vaccine dose in older residents of care homes
Authors: Gokhan Tut, Tara Lancaster, Maria Krutikov, Panagiota Sylla, David Bone, Eliska Spalkova, Christopher Bentley, Umayr Amin, Azar Jadir, Samuel Hulme, Nayandeep Kaur, Elif Tut, Rachel Bruton, Mary Y. Wu, Ruth Harvey, Edward J. Carr, Bobbi Clayton, Sina Namjou, Vanessa Silva, Meghan Poulten, Philip Bawumia, Murad Miah, Samuel Sade, Mauro Miranda, Tom Taylor, Ilenia D’Angelo, Mercedes Cabrera Jarana, Mahbubur Rahman, Janet Abreu, Sandeep Sandhar, Neil Bailey, Simon Caidan, Marie Caulfield, Mary Wu, Ruth Harvey, Lorin Adams, Caitlin Kavanagh, Scott Warchal, Chelsea Sawyer, Mike Gavrielides, Jag Kandasamy, Karen Ambrose, Amy Strange, Titilayo Abiola, Nicola O’Reilly, Philip Hobson, Ana Agau-Doce, Emma Russell, Andrew Riddell, Svend Kjaer, Annabel Borg, Chloë Roustan, Christophe Queval, Rachel Ulferts, Charles Swanton, Sonia Gandhi, Steve Gamblin, Rupert Beale, Oliver Stirrup, Madhumita Shrotri, Borscha Azmi, Christopher Fuller, Verity Baynton, Aidan Irwin-Singer, Andrew Hayward, Andrew Copas, Laura Shallcross, Paul Moss
Journal: Nature Aging (2023)

Abstract Third-dose coronavirus disease 2019 vaccines are being deployed widely but their efficacy has not been assessed adequately in vulnerable older people who exhibit suboptimal responses after primary vaccination series. This observational study, which was carried out by the VIVALDI study based in England, looked at spike-specific immune responses in 341 staff and residents in long-term care facilities who received an mRNA vaccine following dual primary series vaccination with BNT162b2 or ChAdOx1. Third-dose vaccination strongly increased antibody responses with preferential relative enhancement in older people and was required to elicit neutralization of Omicron. Cellular immune responses were also enhanced with strong cross-reactive recognition of Omicron. However, antibody titers fell 21–78% within 100 d after vaccine and 27% of participants developed a breakthrough Omicron infection. These findings reveal strong immunogenicity of a third vaccine in one of the most vulnerable population groups and endorse an approach for widespread delivery across this population. Ongoing assessment will be required to determine the stability of immune protection.
Comprehensive ctDNA Measurements Improve Prediction of Clinical Outcomes and Enable Dynamic Tracking of Disease Progression in Advanced Pancreatic Cancer
Authors: Morten Lapin, Karin H. Edland, Kjersti Tjensvoll, Satu Oltedal, Marie Austdal, Herish Garresori, Yves Rozenholc, Bjørnar Gilje, Oddmund Nordgård
Journal: Clinical Cancer Research (2023)

Circulating tumor DNA (ctDNA) has emerged as a promising tumor-specific biomarker in pancreatic cancer, but current evidence of the clinical potential of ctDNA is limited. In this study, we used comprehensive detection methodology to explore the utility of longitudinal ctDNA measurements in patients with advanced pancreatic cancer.A targeted eight-gene next-generation sequencing panel was used to detect point mutations and copy-number aberrations (CNA) in ctDNA from 324 pre-treatment and longitudinal plasma samples obtained from 56 patients with advanced pancreatic cancer. The benefit of ctDNA measurements to predict clinical outcome and track disease progression was assessed.We detected ctDNA in 35/56 (63%) patients at baseline and found that it was an independent predictor of shorter progression-free survival (PFS) and overall survival (OS). After initiation of treatment, ctDNA levels decreased significantly before significantly increasing by the time of progression. In some patients, ctDNA persistence was observed after the first chemotherapy cycles, and it was associated with rapid disease progression and shorter OS. Longitudinal monitoring of ctDNA levels in 27 patients for whom multiple samples were available detected progression in 19 (70%) patients. The median lead time of ctDNA measurements on radiologically determined progression/time of death was 19 days (P = 0.002), compared with 6 days (P = 0.007) using carbohydrate antigen 19-9.ctDNA is an independent prognostic marker that can be used to detect treatment failure and disease progression in patients with advanced pancreatic cancer.